Critical evaluation of the subcutaneous engraftments of hormone naïve primary prostate cancer.

BACKGROUND

Patient-derived xenografts (PDXs) are considered to better recapitulate the histopathological and molecular heterogeneity of human cancer than other preclinical models. Despite technological advances, PDX models from hormone naïve primary prostate cancer are scarce. We performed a detailed analysis of PDX methodology using a robust subcutaneous model and fresh tissues from patients with primary hormone naïve prostate cancer.

METHODS

Clinical prostate tumor specimens (n=26, Gleason score 6-10) were collected from robotic-assisted laparoscopic radical prostatectomies at Turku University Hospital (Turku, Finland), cut into pieces, and implanted subcutaneously into 84 immunodeficient mice. Engraftments and the adjacent material from prostatic surgical specimens were compared using histology, immunohistochemistry and DNA sequencing.

RESULTS

The probability of a successful engraftment correlated with the presence of carcinoma in the implanted tissue. Tumor take rate was 41%. Surprisingly, mouse hormone supplementation inhibited tumor take rate, whereas the degree of mouse immunodeficiency did not have an effect. Histologically, the engrafted tumors closely mimicked their parental tumors, and the Gleason grades and copy number variants of the engraftments were similar to those of their primary tumors. Expression levels of androgen receptor, prostate-specific antigen, and keratins were retained in engraftments, and a detailed genomic analysis revealed high fidelity of the engraftments with their corresponding primary tumors. However, in the second or third passage of tumors, the carcinoma areas were almost completely replaced by benign tissue with frequent degenerative or metaplastic changes.

CONCLUSIONS

Subcutaneous primary prostate engraftments preserve the phenotypic and genotypic landscape. Thus, they serve a potential model for personalized medicine and preclinical research but their use may be limited to the first passage.

Informations de copyright

2020 Translational Andrology and Urology. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau.2020.03.38). PT reports grants from Academy of Finland, grants from Finnish Cancer Society, during the conduct of the study; personal fees from Roche, outside the submitted work. PJK reports grants from Academy of Finland, during the conduct of the study. PH reports grants from State Research Funding to the responsibility area of Turku University Hospital, during the conduct of the study. The other authors have no conflicts of interest to declare.